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dc.contributor.author
Hafen, Ernst
dc.contributor.author
Okada, Hirokazu
dc.contributor.author
Schittenhelm, Ralf B.
dc.contributor.author
Strässle, Anna
dc.date.accessioned
2018-10-25T09:11:37Z
dc.date.available
2017-06-11T16:59:13Z
dc.date.available
2018-10-25T09:11:37Z
dc.date.issued
2015-03-20
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0113902
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/100016
dc.identifier.doi
10.3929/ethz-b-000100016
dc.description.abstract
The mechanistic target of rapamycin (mTOR) signaling pathway is highly conserved from yeast to humans. It senses various environmental cues to regulate cellular growth and homeostasis. Deregulation of the pathway has been implicated in many pathological conditions including cancer. Phosphorylation cascades through the pathway have been extensively studied but not much is known about the regulation of gene expression of the pathway components. Here, we report that the mRNA level of eukaryotic translation initiation factor (eIF) subunit 4E-binding protein (4E-BP) gene, one of the key mTOR signaling components, is regulated by the highly conserved Ccr4-Not complex. RNAi knockdown of Not1, a putative scaffold protein of this protein complex, increases the mRNA level of 4E-BP in Drosophila Kc cells. Examination of the gene expression mechanism using reporter swap constructs reveals that Not1 depletion increases reporter mRNAs with the 3’UTR of 4E-BP gene, but decreases the ones with the 4E-BP promoter region, suggesting that Ccr4-Not complex regulates both degradation and transcription of 4E-BP mRNA. These results indicate that the Ccr4-Not complex controls expression of a single gene at multiple levels and adjusts the magnitude of the total effect. Thus, our study reveals a novel regulatory mechanism of a key component of the mTOR signaling pathway at the level of gene expression.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Multi-Functional Regulation of 4E-BP Gene Expression by the Ccr4-Not Complex
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS ONE
ethz.journal.volume
10
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0113902
en_US
ethz.size
15 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
006206116
ethz.publication.place
San Francisco, CA, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
ethz.date.deposited
2017-06-11T17:00:00Z
ethz.source
ECIT
ethz.identifier.importid
imp593653184b80143757
ethz.ecitpid
pub:156618
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T02:52:58Z
ethz.rosetta.lastUpdated
2021-02-15T02:17:22Z
ethz.rosetta.versionExported
true
ethz.COinS
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